A double lumen cannula for blood sampling

ABSTRACT

A double lumen cannula instrument for use in withdrawing blood from a patient and having an outer lumen for providing an anticoagulant diluent and an inner lumen for withdrawing blood plus diluent, the body portion of the instrument being approximately one inch long and made of a silastic material. A method and apparatus for separating red cells from plasma in whole blood is also provided in which a diluent is added to whole blood to produce separation of the red cells.

United States Patent [72] Inventor Anthony M. Albisser 52 Wendover Road,Toronto, 18, Canada [211 App]. No. 708,668

[22] Filed Feb. 27, 1968 [45] Patented Oct. 5, 1971 [54] A DOUBLE LUMENCANNULA FOR BLOOD SAMPLING 4 Claims, 6 Drawing Figs.

[52] US. Cl 128/2, 128/214 [51] Int. Cl A6lb 5/00 [50] Field of Search128/2, 214, 214.2, 214.4, 221, 276, 240

[56] References Cited UNlTED STATES PATENTS 2,614,563 10/1952 Devine128/276 3,081,770 3/1963 Hunter 128/221 3,140,714 7/1964 Murphy et al.128/214 3,399,674 9/1968 Pannier et al... 128/214.4 3,470,869 10/1969Fenton et al 128/2 OTHER REFERENCES Weller et al. Annals NY. Acad.Sciences, Vol. 87, 1960, pp. 658- 668 128-2 Primary ExqminerDalton W.Truluck Attorney-Johnson, Marcus & Wray ABSTRACT: A double lumen cannulainstrument for use in withdrawing blood from a patient and having anouter lumen for providing an anticoagulant diluent and an inner lumenfor withdrawing blood plus diluent, the body portion of the instrumentbeing approximately one inch long and made of a silastic material. Amethod and apparatus for separating red cells from plasma in whole bloodis also provided in which a diluent is added to whole blood to produceseparation of the red cells.

PATENIED um 519m SHEET 2 BF 4 I a] .IG/

ANTHONY M. HLBISSER. 6Y:%W,MQL L7.

HGENTS.

A DOUBLE LUMEN CANNULA FOR BLOOD SAMPLING This invention relates todouble lumen cannula instruments, particularly of the type used inpractice and in experimental research on animals and human beings.

ln hospitals and research institutions, it is often necessary towithdraw blood from an animal or a human patient over long intervals oftime and, in some tests, it may even be necessary to withdraw bloodsubstantially continuously for between two to five hours. For example,in metabolic testing a sugar solution is injected into a patient at aregular predetermined rate or at regular predetermined intervals whileat the same time a continuous sample of the patients blood is carriedout. The blood 5 then subjected to certain testing procedures in orderto ascertain its sugar content throughout the period of test. For thispurpose, it is necessary to insert a cannula into the patients vein orartery whereby the blood can be continually withdrawn. In order toprevent coagulation, it is, of course, necessary to provide ananticoagulating diluent and therefore a double lumen cannula instrumentis normally used whereby two concentric tubes are provided, theanticoagulant diluent flowing towards the vein or artery along the outertube whilst the mixture of blood and anticoagulant diluent is withdrawnthrough the inner tube by means of a pumping action. Steps should, ofcourse, be taken to ensure that the anticoagulant diluent does not enterthe blood stream of the patient.

As will be clear from the above discussion, a double lumen cannulainstrument must be provided to permit the anticoagulant diluent to flowtowards the vein or artery to facilitate the withdrawal of the bloodplus diluent away from the vein or artery. The tubes from thediluentsupplying means and the blood-pumping means must be connectedeach to the respective one of the two concentric tubes forming thedouble lumen cannula. In some instances, this has been achieved byobtaining a metal two-way stopcock, welding the handle of the stopcockso that it is in an open position whereby a cannula can be passedthrough the bore thereof for use in withdrawing blood whereby one end isinserted into the vein or artery whilst the other end is connected tothe pump. A plastic sheath was fitted over that end of the cannula whichwas to project into the vein or artery and slid along the externalsurface of the cannula and over the respective part of the stop cock soas to be sealed thereto by means of a sealing compound. A sealingcompound was also sometimes used to seal the cannula to the metal stopcock so as to provide a fluidtight seal. However, in practice, it wasfound extremely difficult to maintain a fluidtight seal and,furthermore, the metallic stopcock was found to be relatively heavyresulting in a discomfort to the patient when used over a long period oftime. The metallic stopcock was found to be cumbersome in use and spaceswithin its body resulted in blood clots being formed in the withdrawnblood.

It is an object of the present invention to provide a double lumencannula instrument which is not as cumbersome as the above-mentionedstopcock instrument, is considerably lighter whereby the discomfortcaused to a patient is not so greater, and wherein there is lesstendency for blood clotting to occur.

Accordingly, there is provided a double lumen cannula instrumentcomprising a mounting of a nonmetallic material, said mounting beingformed with a first bore extending therethrough and of such a diameteras to be capable of receiving a cannula extending through the mounting,the mounting including a second bore extending from the exterior of saidmounting into a cavity at the junction of said first and second bores,said first bore being of one diameter at one end and of a slightlygreater diameter at the other end, whereby when said cannula is inposition in said bore with its penetrating end protruding out of saidother end, a fluid flow is possible from said second bore, into saidcavity within said mounting and out through said other end to theexterior of the mounting.

More specifically, a double lumen cannula instrument according to thepresent invention comprises a body portion made of silastic, said bodyportion including an integral neck portion of silastic, a bore of afirst diameter extending for a first distance towards said neck portionfrom the opposite end of said body and opening into a second bore, saidsecond bore being of a second greater diameter than said first bore andextending from its junction with the first bore towards and through saidneck portion to form an orifice to the exterior of said neck portion, athird bore extending through said body portion from the exterior thereofand opening into said second bore substantially in the region of saidjunction with said first bore, said first diameter being substantiallyequal to the external diameter of an inner-lumen-forming cannula to beused in the instrument so as to provide a fluidtight seal between saidbody portion and the inner-lumen-forming cannula, said neck portionbeing adapted, in use, to receive one end of a plastic cannula sheathconcentric with said inner cannula whereby an outer lumen is formedbetween the external surface of said inner-lumen-forming cannula and theinner surface of said plastic cannula sheath, whereby, in use during thesampling of a patients blood, a anticoagulant diluent can be passedalong said outer lumen to the outer tip of the inner lumen and bloodplus anticoagulant diluent can be withdrawn along said inner lumen.

The overall length of the body portion of the double lumen cannulainstrument may desirably be approximately 1 inch.

An embodiment of the invention will now be described, by way of example,with reference to the accompanying drawings in which:

FIG. I is a diagrammatic representation of a double lumen cannulainstrument according to the present invention;

FIG. 2 is a diagrammatic re cross-sectional view of a mould for formingthe instrument of FIG. 1;

FIG. 3 shows a rod for insertion in the mould of FIG. 2 to ensurecorrect formation of the double lumen cannula instrument;

FIG. 4 is a diagrammatic representation of part of a red cell bloodseparator unit for use with the double lumen cannula instrument as shownin FIG. 1 or independently thereof;

FIG. 5 diagrammatically illustrates a further part of a red cell bloodseparator unit; and

FIG. 6 is a diagrammatic representation of a separator system.

The double lumen cannula instrument as shown in FIG. 1 comprises a bodyportion 1 including an integral neck portion 2 formed as one unit, by amoulding operation, from a mould ing compound, Silastic A" RTV (DowCorning). The overall length of the body portion, including the neckportion, is approximately 1 inch.

During the moulding of the cannula instrument, the body portion 1 isprovided with a bore 3 of a first diameter extending for a firstdistance towards the neck portion 2 from the opposite end 4 of the bodyportion 1. The cannula instrument is also provided with a second bore 5of a second greater diameter, the second bore extending from the region6 of its junction with the first bore 3 and towards the neck portion 2.The bore 5 extends through the neck portion 2 so as to form an orifice 7to the exterior of the neck portion.

The body portion 1 is also provided with a third bore 8 extendingthrough the body portion from the exterior thereof and opening into thesecond bore 5 in the region 6. The third bore 8 is shown substantiallyat right angles to the second bore 5 although this is not, of course,essential to the invention.

In use, a 20 gauge lumen-forming cannula 9, i.e. a smaller diameterstainless steel tube, is inserted into the bore 3 with a substantialpart of its length projecting forwardly of the orifice 7 in the neckportion 2 and a part projecting backwardly from the opposite end of thebody portion 1 whereby a pumping device (not shown) can be attached bysuitable tubing to that end of the lumen-forming cannula 9. It will beappreciated that, in use, the free end of the cannula 9 is inserted intothe vein or artery of a patient whereby blood may be withdrawn forsampling. The blood vessel of a patient is diagrammatically illustratedin FIG. 1 and is identified by the numeral 10.

In FIG. 1, there is also shown a plastic outer lumen sheath ll of amedical cannula which is of such a length that its end projectsapproximately l mm. beyond the end of the inner lumen 9 when the two areinserted into a blood vessel 10. The plastic lumen sheath ll fits ontothe neck portion 2 of the double lumen cannula instrument and because ofthe properties of the silastic material from which the body portion ismoulded, a fluidtight seal .is achieved between the neck portion 2 andthe plastic sheath 11. It will thus be seen that an inner lumen isformed by the lumen-forming cannula 9 while an outer lumen is formedbetween the external surface of the inner lumen-forming cannula 9 andthe inner surface of the concentric plastic lumen-forming cannula sheath1 1.

In use, an 18 gauge stainless steel tube 12 having a length ofapproximately inch is inserted into the third bore 8 so as to form afluidtight seal therewith. Apparatus (not shown) is connected to thestainless steel tube 12 to supply an anticoagulant diluent therealongand along the outer lumen formed between the tube 9 and the sheath 11towards the blood vessel 10. Pumping means (not shown) is connected tothe end of the tube 9 remote from the blood vessel whereby blood may bewithdrawn from the blood vessel for sampling purposes. Due to thepumping action, the anticoagulant diluent is also drawn along the lumen9 which therefore carries a mixture of blood and diluent so thatsubstantially no diluent is passed into the blood vessel 10.

As will be clear from the above, the double lumen cannula instrumentshown in FIG. 1 may conveniently be used in blood-sampling tests on bothhuman patients and animals. Because of the particular construction ofthe lumen cannula instrument and the advantageous medical properties ofthe silastic material used, it has been found that patients find that isis not as cumbersome as the previously used metal cannula instrument andthat during a sampling period of from 2 to 5 hours the silastic cannulainstrument is not as heavy and uncomfortable on the patientss arm as wasthe previously used metal instrument. Further more, it has beenestablished during use that the silastic cannula instrument is not asliable to form clots in the withdrawn blood as was the previously usedmetal cannula instrument. As will be clear, the double lumen cannula isparticularly useful for in vivo study of a patient and permits thecontinuous withdrawal of blood from the respective vein or artery bypermitting the simultaneous infusion of the anticoagulant, which mixesonly with the withdrawn blood, whereby preventing the formation of clotsin the sample tube 9. The mixing of the withdrawn blood and theanitcoagulant occurs only at the tip of the inner lumen 9 which isapproximately 1 mm. inside the input end of the outer tubular sheath 11.Thus, the anticoagulant drawn along the inner lumen 9 does not enter thebloodstream of the patient.

The rate of removal of blood from the patient depends on the difl'erencethe flow rates of the blood sample and the anticoagulant diluent alongthe outer lumen. The solutions may be pumped to and from the cannula bya peristaltic pump-an auto-analyzer proportioning pump, whichestablishes a flow rate dependent on the diameter of the tubing in thepump. This ensures not only that the same volume of blood per unit timeis withdrawn from the patient but also that both flows stop if the pumpis stopped.

Due to the pressure produced by the pump, there is of course moretendency for liquid to leak out of the junctions between the plastic andmetal of the tubes 9 and 12. To avoid this, the bores 3 and 8 may bemoulded during manufacture to be slightly less than the externaldiameter of the respective tube. The bores 3 and 8 may conveniently bemoulded to 0.025 inches, 23 gauge, while the bore 5 may be moulded to be0.036 inch. The undersized bores in a plastic rubber thus ensure a goodpressure fit when the stainless steel tubes are inserted and a goodplastic-to-metal seal is effected which does not leak due to the suctionof the pump.

As mentioned above, the double lumen cannula instrument according to thepresent invention may be included in a system for sampling the blood ofa patient and performing a separation process thereon or alternatively,in instituting certain established test procedures. The sequence ofoperations for withdrawal of whole blood in a continuous monitoringexperiment may be symbolized in block form where the double lumencannula instrument feeds into a block representing withdrawal which alsohas an input from a further block labeled anticoagulant and diluentcapable of supplying the anticoagulant and diluent at a rate R,,. Anoutput from the withdrawal block is fed to a calibration and adjustmentunit at a rate R The calibration and adjustment unit supplies an outputat the rate (R,+R,) to the input of a separator unit. The rate of flow Rrepresents the pumping rate of a further dilution of the blood sample.

The output of the separator unit will consist of two separate outputs,one being a PLASMA output and the other being a RED CELL output.

The sequential operations in the system may be considered as follows:

(1) The continuous withdrawal of blood mixed in situ with ananti-coagulant and diluent.

(2) The calibration and adjustment of the dilution factor volume ofwhole blood R, R A

56ml diluted volume R,+R;

The second part of the double lumen cannula instrument may consist ofthe above described double lumen instrument properly inserted into thefirst part. In practice, the plastic outer lumen sheet 11 will beinserted into the respective blood vessel by means of thetissue-piercing syringe which is normally available for taking a bloodsample and ensuring that one enters the respective blood vessel. Theplastic sheath normally surrounds the needle of the syringe and isinserted into the blood vessel together with the syringe needle. Afterwithdrawing the plunger of the syringe to examine the sampled blood, thesyringe needle is withdrawn while the plastic sheath remains inserted inthe blood vessel. The lumen-forming cannula 9 of FIG. 1 is then merelyinserted down the plastic sheath until it enters the blood vessel insubstitution for the aforesaid needle with the tip of the plastic sheath11 projecting 1 mm. (approximately l/32 inch) beyond the tip of theinner lumen-forming cannula 9 within the blood vessel 10 (FIG. 1). ifnecessary, the two lumen-forming components may be pushed further intothe blood vessel. The pump is now started and the whole blood sample isdrawn into the cannula tip at the rate R at the same time being properlymixed with isotonic diluent and anticoagulant. The diluent is pumped tothe cannula tip along the outer lumen formed by the concentric sheet 11at the rate R,,. The diluted blood is withdrawn from the cannula tip viathe inner lumen at the rate R which is simply the sum of the rates R andR This configuration prevents anticoagulant and diluent from enteringthe bloodstream of the organism.

In one constructed system according to the present inven tion, the bloodsample mixed with anticoagulant and isotonic diluent was drawn from thedouble lumen cannula by means of a peristaltic pump (Techniconproportioning pump-single speed) fitted with a manifold (Techniconmanifold) containing one pump tube (Technicon pump tubes) whose diameterdefined the flow rate R Tygon tubing was used to connect the cannula tothe input of the pump and this should, of course, be kept as short aspossible (between two and three feet) and its internal diameter should,of course, be small-about 0.025 inches. These constraints minimizelongitudinal diffusion in the tubing and also filter the flowirregularities of the peristaltic pumping. Further dilution of the bloodsample can be car- Thus, the rate of the whole blood removal is given bythe formula R,,,,=R,R 1.

During experiments, it has been found the R should preferably be greaterthan 0.l ml./min. in order to minimize the peristaltically inducedfluctuations in the flow R Accurate measurement of the flow rates R and(R,+R can be simply achieved by using two pipettes and a stop watch. Thediluent at flow rate R passes along a path through the proportioningpump rollers to a three-way stopcock capable of passing the diluenteither to waste or into the flow line of the flow at rate R (blood plusanticoagulant diluent), after the respective proportioning pump rollerin the direction flow. When the first-mentioned stopcock is in thecorrect position, the combined flow (R,+R is passed to a furtherthree-way stopcock inserted in the fluid line whereby the fluid flow maybe arranged to enter a 5 ml. pipette.

To measure R,, the flow R is diverted to waste by the firstmentionedstopcock and the flow R is directed into a 2 ml. pipette by means of thesecond-mentioned stopcock. The time to pump a known volume of liquid ismeasured and the flow can be calculated. For the flow (R,+R asmentioned, a 5 ml. pipette is used and by this means both flows can bemeasured.

In FIG. 2, there is shown a mould for manufacturing the silastic cannulainstrument of FIG. 1. The mould may conveniently be a two-piece mouldmade of the plastic referred to as Lucite (registered trade mark). Themould is shown in cross section in FIG. 2 and it will be appreciatedthat prior to drilling and milling the mould, two pieces of Lucite arefitted together and held by means of 3/32 inch studs approximately 1inch long and having a half-round end together with a threaded oppositeend. Conveniently, Lucite blocks may be used having a length severaltimes the size of the required cannula instrument and, for example, aLucite block may be 4- %inch long so that six molds may be drilled andmilled into each block so as to produce the body portions for six doublelumen cannula instruments according to the present invention Thus, twopieces of Lucite material would be required having dimensions7/l6XI-%X4-% inch. The dimensions required for each mould are indicatedin FIG. 2 for convenience, the overall thickness of the moulded bodyportion being arranged to approximately ,4: inch.

Referring to FIG. 2, it will be seen that the mould includes a mainspace 21 within which the main body portion 1 will be formed. The neckportion 2 (FIG. 1) will be formed within the neck space 22 whichcontinues through into a space 23 corresponding to the second bore 5 ofthe double lumen cannula instrument of FIG. 1. The wall of the mould 20is provided with a drilled, or otherwise formed, bore 24 having adiameter of 0.025 inch and emerging into the main space 21 of mould 20.

In FIG. 3, there is shown a rod 25 for insertion within the mould ofFIG. 2 to ensure that the bores 3, 5 and 8 (FIG. 1) are properly formed.The rod 25 is of 1/16 inch diameter and limb total length. At one end itis provided with an axially located bore 26 and a transverse bore 27 asshown in FIG. 3.

During a moulding operation, the end 28 of the rod 25 is inserted in thespace 23 (FIG. 2) with the major portion of the rod 25 projecting intothe space 21. To ensure that the bores 3 and 8 are properly formed, twopieces of wire, such as piano wire, are used. The first piece of wirehaving a diameter of 0.024 inch and a length of approximately 9% inch isinserted in the bore 26 of rod 25 so as to project upwardly through thetop of the mould 20. The second; piece of wire having a diameter of0.024'inch and a lengthof approximately 36 inch is inserted in the bore27 so as to project horizontally through the bore 24 in the mould 20 ofFIG. 2. Thus, when the silastic "A" RTV (Dow Corning) moulding compoundis injected into the mould, the bores 3, 5 and 8 will be properlyformed.

The steps in the moulding operation may be summarized as below. i

1. Ensure that the components of the mould are clean and dry.

2. Assemble the Lucite pieces of the mould together using,

for example, 3/32 inch diameter threaded studs approximately 1V4inchlong.

3. Insert rod or wire into the axially located bore 26 of rod 4. Clampthe assembled combination of rod 25 and the above-mentioned rod or wirewith a pair of hemostats and insert the end 28 of rod 25 into the /5inch diameter hole 23 in the Lucite mould.

5. Align the bore 27 in rod 25 with the 0.025 inch diameter bore 24 inthe mould 20 of FIG. 2.

6. Push the end of the respective rod or wire through the 0.025 inchbore 24 in mould 20 and into the bore 27 of rod 25 (FIG. 3).

7. Prepare the moulding compound, silastic A" RTV (DOW Coring) mouldingcompound, and inject it into the mould, starting at the bottom andfilling the mould to the top so as to ensure that no air bubbles aretrapped by the silastic material.

After the silastic material has properly set and catalyzed,

the mould may be taken apart as follows.

1. Remove the rod or wire from the bore 27 by merely pulling it straightout.

2. Remove the threaded bolts or studs holding the two parts of theLucite mould together.

3. Carefully separate the two parts of the Lucite mould.

4. Remove the silastic double lumen attachment from the Lucite mould.

5. Carefully pull out the remaining rods or wires, i.e. the rod 25 andthe wire previously inserted into the bore 26 thereof.

6. Insert the two pieces of stainless steel tubing 9 and 12 of FIG. 1into the moulded silastic body portion.

The stainless steel tubing constituting the lumen-forming cannula 9 andthe stainless steel tube 12 of FIG. I must be carefully checked toensure that no burrs, fragments of steel, or dirt are introduced intothe final instrument. For the instrument of FIG. 1, the stainless steeltubing 9 should be of 20 gauge and approximately 4 inches long and, instep 6, is passed axially through the moulded body portion. The tube 12should be of 18 gauge stainless steel tubing and approximately 34 inchlong and, in step 6, would be inserted perpendicularly into the mouldedbody portion. In this way, a double lumen cannula instrument as shown inFIG. 1 would be constructed.

Sterilization of the double lumen cannula instrument may be effected byany of the usual methods.

The double lumen cannula instrument described above may conveniently beused for in vivo monitoring of blood parameters in response to drugsand/or other substances in humans or animals. General cannulationsinvolving a double lumen catheter of any length can employ the doublelumen cannula instrument to provide the anticoagulant to the site ofblood removal. Provided that the blood vessel is found and enteredquickly, the procedure in using the described double lumen cannulainstrument is simple and straight forward, taking only a minute or so,and once the pump is started the blood sample may be withdrawncontinuously for as long as necessary and advisable. The double lumencannula instrument has proved, in use, to be both rigid and strong andit has been discovered by experimentation that practical cannulainstruments constructed of the above-mentioned silastic rubber mouldingcompound are particularly useful for medical purposes. Furthermore, thedescribed double lumen cannula instrument may be regard as a disposableitem, for use in one operation only.

Turning now to another aspect, I have designed apparatus for separatingblood by a new method. I

In medical practice and research on animals and humans, it is sometimesnecessary to separate whole blood into its constituent components.Centrifugation methods have previously been used in separators toseparate the respective components from diluted whole blood. As isknown, some chemical analysis must be made on plasma rather than onwhole blood and therefore separated flows, one of diluted plasma and theother of diluted plasma plus the cells, are obtained by separationtechniques so that the appropriate chemical analysis may be made.

By pumping a whole bloodstream into a diluent stream so dilution occurscontinuously, hence dynamically (dynamic dilution), whole blood may beseparated into two laminar streams. The upper stream will consist mainlyof diluent and plasma while the lower stream will consist ofconcentrated red cells and some plasma. In other words, the settlingtime of red cells can be greatly enhanced when a small flow of blood ispumped into another flow of diluent. Settling then occurs in about onesecond and the liquid proceeds in two layers along the tubing of theapparatus used.

In FIG. 4, there is shown a part of a red cell blood separator unit.

The unit shown in FIG. 4 comprises a first part having a cross-sectionalshape as shown so as to form two passageways, a first passageway 31 forthe flow of dilutent and a second passageway 32 for the flow of wholeblood. The passageway 32 joins the passageway 31 at right angles theretoand the output flow of the first part 30 continues in a single flow pathalong an outlet passageway 33 in-line with the passageway 31. Apassageway 34 of a nipple part 35 is provided in-line with thepassageway 31, the part 35 being held in abutting relationship with thepart 30 by means of a Tygon (trade mark name) sleeve 36. A length ofTygon Tubing 37 is provided on end of the nipple part 35 whereby theflow thereto may be fed to subsequent apparatus.

The first part 30 may conveniently be a glass T-fitting type D0 or D1.(Technicon) It is important to note that air segmentation of the streamsis not used because the air bubble tends to remix the blood cells andthe plasma. Separators are effective to remove the lower layer of redcells. In FIG. 5, there is shown a further part of a red cell bloodseparator unit whereby the concentrated red cells and some plasma may beseparated from the partially cell free diluted plasma. The incominglaminar flow of diluted plasma and settled red blood cells travels longa length of tubing 38, through a nipple part 39 and through an in-linepassageway 40 of a further part 41. The nipple part 39 and the furtherpart 41 are held in abutting relationship by means of a sleeve 42.

The combined flow of diluted plasma and settled blood cells travelsalong the passageway 40 into a junction region 43 where the concentratedred cells travel along a lower branch passageway 44 while the partiallycell free diluted plasma travels along an upper branch passageway 45.The concentrated red cells travelling along the lower passageway 44will, in fact, include some plasma therein but by using three cascadedseparator units l have been able to separate in excess of 99 percent ofred cells. This figure is, of course, subject to rechecking.

The partially cell free plasma flowing along passageway 45 may, ofcourse, be passed through a second and then a third separator to furtheraccomplish separation. I believe that the first separator will removealong passageway 40 a volume of fluid corresponding to about twiceexpected red cell volume. Subsequent separators do approximately thesame, but the net flow is less because the red cell concentration hasalready been reduced by the first separator unit.

For proper settling of the whole blood, the tubing connecting eachseparate unit should be preferably maintained horizontal and the locusof its path should be kept smooth with only gradual changes. Smoothtransition along the passageways formed by the respective tubingsinternal diameters and the glass fittings must be maintained to avoidturbulcnce and nonlaminar flow which results in mixing of the twostreams.

A slight downward slope of the whole apparatus should enable the redcells to slide and flow at about the same velocity as the supernatantplasma and diluent.

Obviously, completeness of separation and volume of cell free plasmabear to each other a reciprocal relationship.

At the present moment, I do not have a concrete theoretical explanationof the settling phenomenon. It does, however, occur in solutions at roomtemperatures as well as in ice-water and with diluents as different as0.15 molar NaCl and 0.l5 M LiNO In experiments, isotonic lithium nitratehas been used as a diluent because the lithium ion acts as an internalreference in the flame photometry of sodium and potassium.

It is expected that the flow pattern of the red cells in the small boretubing and the sudden encounter with a new environment, namely that ofthe diluent, causes a change whereby the cells drop out of suspension.To contrast this effect, a well-agitated prediluted sample of bloodsettles slowly very slowly compared to the settling of the cells whendiluted dynamically, i.e. with both solutions in motion. Furtherexperiments should be carried out to appreciate the hydrodynamicproperties of these diluted suspensions of red blood cells.

A chemical analysis of the plasma obtained from the separator unitsdescribed above may be made in a modified autoanalyzer system. Since thesample is prediluted both in the double lumen cannula instrument and atthe first proportioning pump, it is only necessary to modify theauto-analyzer so that further needless dilution doe not take place. Thesimultaneous electrolytes channel of one auto-analyzer determines Na*,K", C1, C0 in the separated plasma; while another auto-analyzer channelmeasures glucose in the separated red cell suspension.

The advantages of the continuous separation technique described aboveare believed to be as follows:

1. The cells are separated anaerobically, rapidly, and continuously.

2. The separation occurs on line as it were.

3. The gravitational stresses applied to the cells are insignificant.

4. The cells are not packed tightly together so that there is lesschance of their contents exchanging with their environment.

5. The separated plasma is removed from the cells almost immediately.

The system also introduces several advantages:

6. The dilution factor can be easily controlled by adjusting 7. The flowrate R of blood withdrawn can be made very small, 0.] ml./min. so thatfrequent measurements may be made.

8. The system is particularly useful in continuous monitoring workbecause it eliminates the need for discrete batch centrifugation andthereby permits complete automation and integration of thewithdrawal-analysis system.

There are also some possible disadvantages:

l. The measured plasma concentration depend on the sample hematocritbecause the whole blood is diluted first and then separated; in contrastto first separating the plasma from the cells and then diluting theplasma for analysis. The latter method is believed to introduce nohematocrit dependence.

The described separator method and apparatus may be used in conjunctionwith the double lumen cannula instrument illustrated in HO. 1 or,alternatively, it may be used separately therefrom or with othersuitable apparatus.

1 have constructed a multiple separation unit for continuous separationusing pieces of glass and tubing, etc. manufactured by the TechniconCompany.

The arrangement is shown diagrammatically in FIG. 6 and it will be seenthat heparinized, diluted whole blood fiow from a double lumen cannulainstrument, such as shown in FIG. I, is fed along one input line whilean isotonic diluent NaCl or LiNO is fed along another input line. Theflow rates at various parts of the arrangement are indicated in ml./min.and a Technicon proportioning pump is utilized to ensure continuousblood withdrawal. The pump tube shoulder colors are indicated on therespective lines.

Identification of the respective parts in FIG. 6 is indicated in thefollowing list.

(A) Tygon tubing 0.065" I.D. Length, 4 ft. minimum (B) Tygon tubing0.065 I.D. Length, 8 in. minimum Tygon tubing 0.065" I.D. Length, 8 in.minimum The interconnecting tubes A, B and C serve the additionalpurposes of maintaining laminar flow as well as allowing settling of thered cells. It is necessary that they be placed to avoid any sharp bendsor twists which would cause mixing of the two ribbons of fluid in thetubes.

All connections should be made properly using the appropriate nipples sothat laminar flow is maintained throughout.

The red cell collecting tubes should be adjusted in length and internaldiameter so that the three flows are in phase at the summation point Z.In this way, an analysis, such as glucose, performed on the red cellsuspension will not suffer from excessive mixing or loss of response toa step change in concentration.

To maintain the response of the separators it is also advantageous toplace the separators in a descending cascade allowing the more viscousred cells to slide down a ramp thereby maintaining equal the velocity ofboth separated streams.

For different conditions, different pump tubes may be used. Perhaps onlytwo instead of three separators need be used. The configuration shown isnot necessarily the best; it removes better than 99 percent of the redcells, but proper adjustment of the orientation and settling lengths canincrease this figure.

lclaim:

1. In a blood sampling apparatus, a double lumen cannula instrumentcomprising:

a. a body portion molded from silastic;

b. said body portion including a integral neck portion of silastic andof smaller cross-sectional area than said body portion;

c. a first bore of a first diameter extending for a first distancetowards said neck portion from the opposite end of said body and openinginto a second bore;

d. said second bore being of a second greater diameter than said firstbore and extending from its junction with the first bore towards andthrough said neck portion to form an orifice to the exterior of saidneck portion;

e. an inner-lumen-forming cannula extending through said first andsecond bores;

f. said first diameter being substantially equal to the externaldiameter of the inner-lumen-forrning cannula so as to provide afluidtight seal between said body portion and the inner-lumen-formingcannula;

g. a third bore extending through said body portion from the exteriorthereof and opening into said second bore substantially in the region ofsaid junction of said first bore and a tubular member in said third borehaving one end emerging into said region and the other end extending tosaid exterior of the body portion; a plastic cannula sheath concentricwith said Inner cannula and having one end fitting over said neckportion whereby an outer lumen is formed between the external surface ofsaid inner-lumen-forming cannula and the inner surface of said plasticcannula sheath;

g. whereby, in use during the sampling of a patient's blood ananticoagulant diluent can be passed along said outer lumen to the outertip of the inner lumen and blood plus anticoagulant diluent can be withdrawn along said inner lumen.

2. A cannula according to claim 1 wherein the oval length of the bodyportion of the double lumen cannula instrument is approximately 1 inch.

3. A double lumen cannula instrument according to claim I wherein saidthird bore is at right angles to said first bore.

4. A double lumen cannula instrument according to claim 3 wherein saidtubular member is a stainless steel tube inserted in said third bore.

1. In a blood sampling apparatus, a double lumen cannula instrumentcomprising: a. a body portion molded from silastic; b. said body portionincluding a integral neck portion of silastic and of smallercross-sectional area than said body portion; c. a first bore of a firstdiameter extending for a first distance towards said neck portion fromthe opposite end of said body and opening into a second bore; d. saidsecond bore being of a second greater diameter than said first bore andextending from its junction with the first bore towards and through saidneck portion to form an orifice to the exterior of said neck portion; e.an inner-lumen-forming cannula extending through said first and secondbores; f. said first diameter being substantially equal to the externaldiameter of the inner-lumen-forming cannula so as to provide afluidtight seal between said body portion and the inner-lumenformingcannula; g. a third bore extending through said body portion from theexterior thereof and opening into said second bore substantially in theregion of said junction of said first bore and a tubular member in saidthird bore having one end emerging into said region and the other endextending to said exterior of the body portion; h. a plastic cannulasheath concentric with said inner cannula and having one end fittingover said neck portion whereby an outer lumen is formed between theexternal surface of said inner-lumen-forming cannula and the innersurface of said plastic cannula sheath; g. whereby, in use during thesampling of a patient''s blood an anticoagulant diluent can be passedalong said outer lumen to the outer tip of the inner lumen and bloodplus anticoagulant diluent can be with drawn along said inner lumen. 2.A cannula according to claim 1 wherein the oval length of the bodyportion of the double lumen cannula instrument is approximately 1 inch.3. A double lumen cannula instrument according to claim 1 wherein saidthird bore is at right angles to said first bore.
 4. A double lumencannula instrument according to claim 3 wherein said tubular member is astainless steel tube inserted in said third bore.